Recent studies show that gastrointestinal hormones/growth factors may stimulate cell growth by stimulating multiple intracellular tyrosine phosphorylation (TyrP) signaling cascades as well as by transactivating growth factor receptors. However at present little is known about the ability of many gastrointestinal hormones/growth factors to activate these cascades. Our studies have been in two general areas, which include studies of intracellular signaling cascades primarily by tyrosine kinases and studies of tumoral growth attempting to develop novel agents for growth inhibition. Recent studies show that gastrointestinal hormones, similar to growth factors, may stimulate cell growth/cell signaling by stimulating multiple intracellular tyrosine phosphorylation (TyrP) cascades. Whereas these cascades have been extensively investigated with growth factors, little is known in this area with may gastrointestinal hormones. The goal of these studies is to clarify this area primarily concentrating on cholecystokinin receptor cascades and bombesin receptor activation using primarily pancreatic acini as a model natural cell system as well as to study the role of gastrointestinal hormones in stimulating tumor growth(primarily lung cancer ). In four different studies activation of Bn-related receptors (BRS-3) as well as PACAP receptors on lung cancer cells were found to stimulate tumor growth and the mechanism involved transactivation of the EGF receptor as well as stimulating activation of p125FAK, paxillin and PYK2 in addition to activation of reactive oxygen species, matrix metalloproteinases and Src. In pancreatic acini, CCK and other PLC activating hormones was shown to activate the Src kinase YES and its activation to play an important role in activating other key signaling cascades stimulated by CCK. In collaboration with Prof Ito, Fukuoka, Japan, cytosolic double-stranded DNA was shown to show a damage-associated molecular patten that induced the inflammatory response in pancreatic stellate cells and to be a plausible mechanism for tissue injury-associated pancreatitis. .